Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001323289.2(CDKL5):c.454T>C (p.Cys152Arg)

CA412351039

658951 (ClinVar)

Gene: CDKL5 (HGNC:6792)

Condition: CDKL5 disorder (MONDO:0100039)

Inheritance Mode: X-linked inheritance

UUID: c46cc2df-17be-4942-8afe-fa2db0c1c722

Approved on: 2023-04-14

Published on: 2023-06-16

HGVS expressions

NM_001323289.2(CDKL5):c.454T>C (p.Cys152Arg)

NM_001323289.2:c.454T>C

NC_000023.11:g.18581941T>C

CM000685.2:g.18581941T>C

NC_000023.10:g.18600061T>C

CM000685.1:g.18600061T>C

NC_000023.9:g.18509982T>C

NG_008475.1:g.161337T>C

ENST00000623535.2:c.454T>C

ENST00000635828.1:c.454T>C

ENST00000637881.1:c.454T>C

ENST00000674046.1:c.454T>C

ENST00000379989.6:c.454T>C

ENST00000379996.7:c.454T>C

ENST00000463994.4:c.454T>C

ENST00000623535.1:n.454T>C

NM_001037343.1:c.454T>C

NM_003159.2:c.454T>C

NM_001323289.1:c.454T>C

NM_001037343.2:c.454T>C

NM_003159.3:c.454T>C

Likely Pathogenic

PP3 PM5 PM6 PM2_Supporting

Evidence Links 0

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Cys152Arg variant in CDKL5 occurs in the de novo state (biological parentage unconfirmed) in an individual (GeneDx Internal Database) (PM6). The p.Cys152Arg variant in CDKL5 is absent from gnomAD (PM2_supporting). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). A pathogenic missense variant (p.Cys152Phe) has been previously identified within this codon which indicates that this residue is critical to the function of the protein (PMID 15499549; 23651931) (PM5). In summary, the p.Cys152Arg variant in CDKL5 is classified as likely pathogenic for CDKL5-related disorders based on the ACMG/AMP criteria (PM6, PM2_supporting, PP3, PM5).

PP3

Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own.

PM5

A pathogenic missense variant (p.C152F) has been previously identified within this codon which indicates that this residue is critical to the function of the protein (PMID 15499549; 23651931)

PM6

The p.Cys152Arg variant in CDKL5 occurs in the de novo state (biological parentage unconfirmed) in an individual (GeneDx Internal Database)

PM2_Supporting

The p.Cys152Arg variant in CDKL5 is absent from gnomAD

Curation History

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